Cancer Cell, Volume 32 Supplemental Information A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-ptpn14-yap Axis in Pancreatic Cancer Stephano S. Mello, Liz J. Valente, Nitin Raj, Jose A. Seoane, Brittany M. Flowers, Jacob McClendon, Kathryn T. Bieging-Rolett, Jonghyeob Lee, Danton Ivanochko, Margaret M. Kozak, Daniel T. Chang, Teri A. Longacre, Albert C. Koong, Cheryl H. Arrowsmith, Seung K. Kim, Hannes Vogel, Laura D. Wood, Ralph H. Hruban, Christina Curtis, and Laura D. Attardi
Well differentiated Moderately differentiated Poorly differentiated Ck19 H&E 3 µm Figure S1, related to Figure 1. Differentiation states in mouse PDAC Representative H&E and Ck19 immunostaining images showing pancreatic cancers of various differentiation states in 3 different Kras +/LSL-G12D,Pdx1-Cre,p53 +/LSL-25,26,53,54 mice. The scale bar applies to all images in the panel.
18 PTPN14 expression relative to ACTB 9 p53 WT p53 KO Figure S2, related to Figure 3. Ptpn14 expression is p53-dependent in human colorectal cancer cells qrt-pcr analysis of PTPN14 expression in doxorubicin-treated (.2 µg/ml) human HCT116 colorectal cancer cells with and without p53 (n=2). The cells were collected 24 hr post-treatment. PTPN14 expression ± SD is shown relative to ACTB.
A Panc1 Antigen BrdU Merge MIA PaCa-2 Antigen BrdU Merge PTPN14 p53 GFP PTPN14 p53 GFP 3 µm 3 µm B shcont shptpn14-1 Ptpn14 p53 Figure S3, related to Figure 4. Ptpn14 inhibits cell proliferation in human pancreatic cancer cells (A) The effect of HA-GFP, HA-Ptpn14 or HA-p53 expression on cell cycle progression in PANC-1 and MIA PaCa-2 human PDAC cells was examined by BrdU immunostaining. BrdU-positivity of cells expressing each antigen (detected by green fluorescence or HA immunofluorescence) was assessed. Representative images with arrows pointing to BrdU + cells and arrowheads pointing to BrdU - cells are depicted. The scale bar applies to all images in the panel. (B) Western blot examining Ptpn14 levels in p53-overexpressing PDAC cells from Kras +/LSL-G12D ;Pdx1-Cre;Trp53 fl/fl (KPC) mice which were also transduced with either shcontrol or shptpn14-1. The cells were used for BrdU incorporation experiments (quantification shown in Figure 4E). Actb is a loading control. Actb
A Expression relative to Actb 1.2.8.4 shcont shp53 KIC1 Ptpn14 Trp53 shptpn14-1 KIC2 shptpn14-2 Ptpn14 Trp53 B Low plating Soft agar shcont shp53 shptpn14-1 shptpn14-2 C Number of colonies 24 16 8 shren shptpn14 shptpn14 + PMGIB empty shptpn14 + PMGIB Ptpn14 shptpn14 shren PMGIB: Ptpn14 empty - - Figure S4, related to Figure 5. Ptpn14 displays tumor suppressor activity (A) qrt-pcr to examine knockdown of Ptpn14 in two different lines of PDAC cells from Kras LSL-G12D/+ ;Pdx1-Cre;Cdkn2a fl/fl (KIC) mice after infection with a luciferase control shrna or either of two Ptpn14 shrnas (n=3). The graph shows the average expression value ± SD relative to Actb. Knockdown of Trp53 with p53 shrna is also shown. (B) (Upper) Representative images of low plating experiments in a second KIC cell line after introduction of control shrna, p53 shrna, Ptpn14 shrna-1 or Ptpn14 shrna-2 (n=3, quantification shown in Figure 5B). (Lower) Representative images of soft agar experiment in a second KIC cell line after introduction of luciferase control shrna, p53 shrna, Ptpn14 shrna-1 or Ptpn14 shrna-2 (n=3, quantification shown in Figure 5C). (C) (Left) Low plating experiment quantification, showing the average colony number ± SD after introduction of luciferase control shrna, p53 shrna, Ptpn14 shrna-1 or Ptpn14 shrna-2, and rescue with a PMGIB-Ptpn14 overexpression construct. The experiments were performed in two PDAC KIC cell lines (n=2). (Right) Representative images show the crystal violet-stained colonies 2 weeks after seeding. p.5; p.1, based on the two-tailed unpaired Student's t-test.
KIC - - + Yap 1..42 1.36.51 Actb C Empty Ptpn14 WT E 18 KPC + 4 12 6 KIC KPC shcont Ptpn14C1121S 25 8 GFP Ptpn14 WT Ptpn14 C1121S 5 12 shyap shyap C shcont shyap shcont shyap Ptpn14 WT N D 75 Number of colonies B Number of colonies Merge GFP Ptpn14 WT Ptpn14 C1121S BrdU GFP Tag Cells with Yap nuclear exclusion (%) A KPC PPxY KIC KPC 15 µm Figure S5, related to Figure 6. Ptpn14 inhibits proliferation through effects on Yap activity (A) HA-GFP or different Ptpn14 variants were expressed in Kras+/LSL-G12D;Pdx1-Cre;Trp53fl/fl (KPC) mouse PDAC cells and BrdU-positivity of cells expressing each antigen (detected by green fluorescence or V5/HA immunofluorescence) was assessed. Representative images with arrows pointing to dividing (BrdU+) cells and arrowheads pointing to arresting (BrdU-) cells are depicted. The scale bar applies to all images in the panel. (B) Effects of HA-Ptpn14 or the phosphatase mutant HA-Ptpn14-C1121S expression on Yap localization in KPC cells, compared to HA-GFP. The graph shows the percentage of cells with Yap nuclear exclusion +/- SD (n=3). At least 5 cells were analyzed per experiment (C) Colony forming ability of KPC cells overexpressing HA-Ptpn14 or the phosphatase mutant HA-Ptpn14-C1121S. (Left) Low plating experiment quantification, showing the average colony number ± SD (n=3). (Right) Representative images show the crystal violet-stained colonies 2 weeks after seeding. (D) Western blot confirming knockdown of Yap protein in PDAC cells from KIC and KPC cells after introduction of a luciferase control shrna or a Yap shrna. Actb is a loading control. (E) Colony forming ability of KIC and KPC cells expressing luciferase control or Yap shrnas. (Left) Low plating experiment quantification, showing the average colony number ± SD (n=3). (Right) Representative images show the crystal violet-stained colonies 2 weeks after seeding. p.5; p.1, based on the two-tailed unpaired Student's t-test.
Table S1, related to Figure 6. List of 42 Yap target genes depicted in heatmap on Figure 6G. 1 Rgcc 2 Tgm2 3 Serpine1 4 Phgdh 5 Ndrg1 6 Tnnt2 7 Schip1 8 Slit2 9 Fstl1 1 Lhfp 11 Axl 12 Camk4 13 Hexb 14 Msn 15 Dut 16 Itgb5 17 Tk1 18 Cdk6 19 Shcbp1 2 Anln 21 Sgk1 22 Samsn1 23 Mdfic 24 Shisa4 25 Stmn1 26 Ccrn4l 27 Cdc2 28 Cenpf 29 Birc5 3 Top2a 31 Hmmr 32 Rpn2 33 Mocs2 34 Nras 35 Siae 36 Gas2l3 37 Dram2 38 Ect2 39 Thbs1 4 Rhoq 41 Msrb3 42 Ctgf
A KRAS MUT PAAD COAD OV LAML LUSC LUAD BRCA UCEC READ KRAS WT PAAD COAD OV LAML LUSC LUAD BRCA UCEC READ 1 2 Fold change (p53 MUT vs. p53 WT) CDC2 MTHFD2 PSAT1 PHGDH SLC7A5 CENPF ANLN BIRC5 STMN1 SHCBP1 NDRG1 BAIAP2L2 TOP2A KCNK12 ECT2 COL4A3 TK1 FSCN1 HMMR GGH GPT2 MSN CDK6 DLX5 GAS2L3 GLS CDKN2C SLC3A2 BCAT1 FUT8 SEMA3C GDF15 GOLGA2B CYP4B1 SHISA4 SIAE SNAP23 TSPYL3 DDB2 E 8 6 4 2 Number of colonies C OS..2.4.6.8 1. B RFU % Viable fold-change Cells Empty Ptpn14 HCT116 WT HCT116 KO 8 4 Empty HCT116 p53 wt HCT116 p53-/- HCT116 WT HCT116 KO Ptpn14 DMSO verteporfin (1 µm) Logrank p= 9.4E 2 % Viable Cells 12 6 CAPAN2 high low 365 73 195 No. At Risk time (days) high 18 13 6 2 low 18 11 3 MIAPACA CAPAN2 MiaPaCa % Viable Cells HCT116 WT HCT116 KO 4 2 A549 12 Number of colonies D H1299 % Viable Cells A549 H1299 9 6 3 5 2.5 MCF7 MDA-MB-231 Cox Proportional Hazards Overall Survival 3y p value.59 PTPN14 exp 7.58 : 6.94 PTPN14 cn.11:.2 AGE 74:6 TP53 MUT:WT STAGE I:II STAGE IV:II GRADE G3:G2 GENDER fem:mal KRAS WT:MUT Empty Ptpn14 A549 H1299 MCF7 MDA-MB-231 Empty Ptpn14 No Event 25 Event 29 A549.1.75 1.5 2.5 3.5 4.5 Improved survival Decreased survival Figure S6, related to Figure 7. The p53-ptpn14-yap tumor suppressive axis is important in human cancer (A) Heat map illustrating the fold-change in the expression of Yap-activated genes in tumor samples harboring TP53 mutations relative to tumors with wild-type TP53. For each cancer the samples were further divided into those expressing mutant and wild-type KRAS (except OV and LAML, where there are no KRAS mutations), to assess the effect of KRAS mutations on p53-dependent Yap inhibition. (B) Quantification of viable cells using the Cell Titer-Blue assay in a variety of p53-proficient and deficient human cancer cells treated with DMSO or the Yap inhibitor verteporfin (1 µm). Colorectal (HCT116 p53 WT and HCT116 p53 KO), pancreatic (CAPAN2-p53 WT and MIA PaCa-2-p53 MUT), lung (A549-p53 WT and H1299-p53 MUT) and breast (MCF7-p53 WT and MDA-MB-231-p53 MUT) cancer cells were assessed 48 hours after verteporfin treatment (n=5). The Relative Fluorescence Units (RFU) reads ± SD were normalized based on initial fluorescence and background fluorescence values. (C) Colony formation ability of HCT116 cells proficient or deficient for p53 after introduction of a plasmid expressing HA-Ptpn14. (Left) Low plating experiment quantification, showing the average colony number ± SD (n=3). (Right) Representative images show the crystal violet-stained colonies 2 weeks after seeding. (D) Colony formation ability of A549 (p53 wild-type) or H1299 (p53 mutant) cells after introduction of a plasmid expressing HA-Ptpn14. (Left) Low plating experiment quantification, showing the average colony number ± SD (n=2). (Right) Representative images show the Crystal Violet-stained colonies 2 weeks after seeding. (E) Analysis of overall survival of PDAC patients from the International Cancer Genome Consortium (ICGC) pancreatic cancer project (Code: PACA-AU) divided by PTPN14 expression levels. (Left) Kaplan-Meier analysis for overall survival of patients with tumors manifesting either high or low expression values of PTPN14. Survival analysis was based on those individuals without PTPN14 copy number variations. High value correspond to the high tercile of the adjusted expression value, and low value to lowest tercile. (Right) Hazard plot of Cox Proportional Hazards for the association between overall survival and PTPN14 expression levels, CN, grade, age, stage, gender and KRAS and TP53 mutation status. Asterisks indicate the factors that significantly affect overall survival. H1299
Table S2, related to Figure 7. Sample size for each cohort and breakdown of TP53 mutant vs TP53 wild-type cases used to determine changes in gene expression of Yapinduced genes, in Figure 7C. Cancer type Dataset Total p53 wild-type p53 mutant Rectum adenocarcinoma READ 35 14 21 Colon adenocarcinoma COAD 65 31 34 Ovarian serous cystadenocarcinoma OV 162 7 155 Lung squamous cell carcinoma LUSC 177 36 141 Lung adenocarcinoma LUAD 163 82 81 Breast invasive carcinoma BRCA 751 498 253 Bladder urothelial carcinoma BLCA 95 47 48 Kidney renal clear cell carcinoma KIRC 391 383 8 Head and Neck squamous cell carcinoma HNSC 271 75 196 Glioblastoma multiforme GBM 142 97 45 Uterine Corpus Endometrial Carcinoma UCEC 239 171 68 Acute Myeloid Leukemia LAML 169 156 13 Pancreatic adenocarcinoma PAAD 121 4 81
Table S3, related to Figure 7. Combined statistics of Yap-induced genes, comparing expression levels in TP53 mutant and TP53 wild-type samples across different types of cancer, for each gene shown in Figure 7C. symbol entrez hazard ratio coef se lower upper p value CDC2 991 2.9423592.73987379.449542 1.91759993 2.28667864 7.6E-7 DDB2 1643.57681272 -.5523876.2836685.54561768.6978993 1.96E-62 MTHFD2 1797 1.6185652.4815197.328893 1.51746151 1.72626742 1.68E-48 PSAT1 29968 2.18227848.745847712.6237312 1.86562972 2.38237235 7.73E-47 PHGDH 26227 2.13141535.756188426.5882446 1.89817823 2.3945148 4.4E-46 SLC7A5 814 1.87768378.6338986.558943 1.68284896 2.957594 1.99E-45 CENPF 163 1.663376468.58849554.455483 1.5214468 1.81854619 1.5E-44 ANLN 54443 1.7667926.565694945.45798 1.695144 1.9262322 8.85E-44 BIRC5 332 1.839817143.69666188.4843366 1.67321 2.232599 9.34E-43 STMN1 3925 1.571826328.45223829.3977591 1.45394254 1.69926798 1.6E-4 SHCBP1 7981 1.53228936.425417356.389874 1.4176726 1.6517217 1.13E-37 SEMA3C 1512.743242314 -.29673316.593436.6623399.8344125 6.7E-35 NDRG1 1397 1.533696421.42768783.5142128 1.38665855 1.69632583 4.81E-34 FUT8 253.79862745 -.22486911.371925.74259691.85887119 1.21E-31 BAIAP2L2 8115 1.7685119.57138459.6797384 1.5479212 2.253989 7.64E-3 GDF15 9518.389564551 -.9427257.7839485.3347933.45426497 3.89E-29 TOP2A 7153 1.476531596.389695821.4657222 1.34772226 1.61765196 4.43E-25 GOLGA2B 55592.58577465 -.536112.4864919.5318677.64361126 1.21E-24 KCNK12 5666 1.841883996.61788959.583998 1.64267736 2.6524832 2.5E-24 ECT2 1894 1.429318723.357197913.3844948 1.32556438 1.5411941 2.26E-24 COL4A3 1285 1.518993871.41848189.799713 1.29862738 1.77675476 2.99E-24 TK1 783 1.5869674.411245751.4213628 1.3891569 1.63858219 5.34E-24 CYP4B1 158.72634251 -.321589.6455541.6397458.82396123 2.24E-23 FSCN1 6624 1.56748183.4494742.4746944 1.42822443 1.7231736 2.33E-23 HMMR 3161 1.493797566.4132158.4728785 1.3615788 1.63886522 4.79E-23 SHISA4 149345.856474549 -.1549368.416797.789297.92937778 2.53E-22 GGH 8836 1.47337757.34169984.478529 1.28134441 1.54571991 6.28E-22 SIAE 54414.68635571 -.3768258.378768.63695164.7389195 1.77E-21 GPT2 8476 1.4434945.364667381.4333849 1.32276667 1.56769949 3.6E-21 MSN 4478 1.26445113.231464923.336569 1.18134942 1.34483656 6.6E-21 SNAP23 8773.855321243 -.15627816.28519.82114499.8991991 7.57E-21 CDK6 121 1.5182841.41758756.512119 1.37328937 1.67858748 2.76E-19 DLX5 1749 1.615782962.479819645.738531 1.3984621 1.8674382 4.83E-19 GAS2L3 283431 1.369986422.3148829.5232951 1.2364474 1.51795613 5.26E-19 TSPYL3 128854.782662148 -.2455416.494982.7129929.8623978 1.38E-17 GLS 2744 1.28689474.252165879.351741 1.2145464 1.37822817 3.53E-17 CDKN2C 131 1.235226491.211254347.411371 1.13961736 1.33885682 4.89E-17 SLC3A2 652 1.284518259.25383753.2741842 1.21731137 1.35543559 8.1E-17 BCAT1 586 1.52464242.4213861.6238223 1.34866295 1.72227747 9.8E-17 C16orf87 388272 1.27163929.2436847.282376 1.231895 1.34398371 4.1E-16 C17orf58 28418.9149214 -.1374.316528.8472645.9591944 4.47E-16 ASAP1 587 1.3324624.2867127.3145 1.2559551 1.4127456 9.67E-16 CRIM1 51232.8818829 -.12659753.399926.8168996.9512633 1.77E-15 XAGE2 952 1.95832883.91514697.25781 1.52515 1.1493358 4.3E-15 SCHIP1 2997 1.395684567.33338524.431163 1.28284951 1.51844421 7.56E-15 SDPR 8436.68262944 -.38263333.69657.6524456.76863121 9.4E-15 PRRG1 5638 1.313755689.272889974.4656698 1.19915888 1.4393386 2.3E-14 ATP2C1 2732 1.129596671.12186641.217155 1.8389513 1.17722518 6.31E-14 GNB4 59345 1.213455177.19347189.428393 1.12133144 1.3131474 1.25E-13 DLC1 1395.68767249 -.37444585.4617651.62816642.7528165 1.47E-13 MYC 469 1.4575143.37672362.4734415 1.328341 1.599227 2.98E-13 RPN2 6185 1.1879282.17156688.2331236 1.1347268 1.2425921 5.59E-13 TNNT2 7139 1.18149987.16678478.5658898 1.5746269 1.328623 6.95E-13 PMP22 5376.7823429 -.2481613.446778.71481758.85163763 5.64E-12 GKAP1 8318.763586 -.274366.3982253.757595.82499336 5.69E-12 ITGB5 3693.94758912 -.5439398.3618247.8822238 1.1665962 5.96E-12
ETV5 2119 1.19916898.1816226.4524258 1.974493 1.313521 2.24E-11 DUSP1 1843.693222327 -.3664451.5653462.62512.7744527 2.29E-11 CDIPT 1423 1.1886152.1827324.293783.972417 1.5323324 3.67E-11 MYO1C 4641.86497694 -.1455341.271458.8216645.91223391 4.91E-11 TRIB3 57761 1.462237681.379967921.463325 1.3353843 1.6123233 6.77E-11 MOCS2 4338.799114381 -.22425119.278979.7565942.8442438 7.16E-11 AGFG2 3268.8333544 -.18593141.317582.78126654.8824758 1.32E-1 FLNA 2316 1.33321344.28758376.4358647 1.2243792 1.45213 1.67E-1 NUAK2 81788.979437217 -.277714.414376.939545 1.6223242 2.1E-1 FAF2 23197.915519433 -.8826369.1815191.883525.94867728 1.17E-9 ARHGAP29 9411 1.52772775.51427422.4692835.962671 1.15419751 1.42E-9 MARCKS 482 1.246322358.2219711.3355461 1.1669947 1.3314311 2.43E-9 CXorf56 63932 1.197974491.1863226.2263583 1.14598759 1.25231974 4.57E-9 C8orf48 157773.8887779 -.21219399.5993774.71916115.9962925 5.22E-9 SLIT2 9353.9746149 -.9756195.7325861.78572676 1.479774 5.98E-9 GLIS2 84662 1.947684.9535929.4147712 1.928512 1.18747545 6.15E-9 TNS1 7145.85873724 -.15233132.4281859.78957992.93387898 8.49E-9 RHOQ 23433 1.14376498.134324664.279565 1.827794 1.28184 1.35E-8 ANKRD1 2763 1.146212487.13646318.8261426.97486337 1.34767918 1.67E-8 AMOTL2 51421 1.74567893.71918621.3661467 1.15521 1.15451697 3.15E-8 EDN2 197 1.157424463.146197246.768133.99565595 1.34547621 3.92E-8 PPP1R3B 7966.822554929 -.195342.445633.7598597.8943331 8.71E-8 THBS1 757.881475213 -.1261584.544967.79217737.9883912 1.E-7 FAM167A 83648.9819491 -.182682.6992941.85614122 1.12614276 1.6E-7 LHFP 1186.8749185 -.21382232.411765.74488466.87536114 3.54E-7 NEB 473 1.45891892.377695695.6933692 1.2735367 1.67128627 4.52E-7 NRAS 4893 1.1568759.14359597.2752856 1.924736 1.21447828 4.79E-7 MAML2 84441 1.223727454.2191491.471695 1.11566537 1.34225631 6.44E-7 TSPAN3 199.883693267 -.12364526.2761151.8371495.93283429 6.7E-7 EDN1 196 1.17925793.164879315.59262 1.54238 1.3238818 7.37E-7 ITGB2 3689 1.1758964.161343944.538996 1.573118 1.359993 1.11E-6 FLOT1 1211.998454663 -.154653.25168.9541231 1.4892551 1.21E-6 TGM2 752 1.221716949.225725.533764 1.136517 1.35645179 1.36E-6 TEAD1 73.94857246 -.5279754.3199995.89966 1.99759 1.41E-6 GTPBP3 8475 1.193333929.17675111.2679268 1.13228569 1.25767364 1.85E-6 SEC14L1 6397 1.66248312.64146237.266572 1.119716 1.12343773 1.93E-6 SLC5A3 6526 1.1489342.1388761.3753393 1.674178 1.2366876 1.95E-6 AKR1C2 1646 1.255814814.227784616.15855 1.312744 1.5292551 2.E-6 DDAH1 23576.89916886 -.2182365.384147.75172588.87261245 2.28E-6 HEXB 374.892295556 -.11395786.2437499.8566919.93595886 5.63E-6 GAS6 2621.86455485 -.14554558.45245.79125354.94463721 5.84E-6 TGFB2 742 1.148844124.138756327.6592214 1.95977 1.3729661 1.79E-5 MSRB3 253827.82569957 -.19163282.524956.74488733.915841 3.15E-5 GADD45B 4616.827712529 -.1898937.49348.76389977.89685592 3.45E-5 TMEM49 81671.921936813 -.8127859.2793621.87281422.9738246 4.17E-5 FAM35A 54537.919459876 -.8396887.2181562.8897441.95962659 4.52E-5 ARHGEF1 9639.9492159 -.689555.378115.87496336 1.1185184 5.55E-5 C8orf58 541565.89281688 -.1133872.26945.84688366.94122837 6.78E-5 SH2D4A 63898.713913338 -.3369937.4787515.64997117.78414594.178 SAMSN1 6492 1.2352418.2325175.5352814.92158388 1.1367453.258 MDFIC 29969.977932235 -.223149.3962498.9485692 1.56993.289 EMP2 213.893456417 -.11265772.457818.8251549.96741671.584 MACF1 23499.95392312 -.4717514.3148541.89683318 1.1464128.64 SNX7 51375 1.5257141.5117571.3619679.9842481 1.1298898.926 CCDC8 83987.98581655 -.196936.6667872.8645217 1.11748266.955 DAB2 161.92345114 -.7963743.428688.8493292 1.43928.989 SFRS2IP 9169.919615549 -.8379958.219473.8896968.95995671.139 GOLGA7 51125 1.3284246.32314672.2756697.97851849 1.918231.1823 CNIH 1175.9647279 -.3665643.25586.91789983 1.124377.1853 SERTAD4 56256 1.161193494.14944835.6317691 1.25955 1.31425875.1855 RAB4C 57799.9137873 -.916536.2833216.8644299.96595759.195
SGK1 6446 1.57896935.56282914.441555.9719298 1.15352919.276 ORC2L 4999 1.5613556.5597859.2467.9667218 1.4677337.2361 SLC38A1 81539 1.5394177.52536545.41414.9717995 1.1432622.3289 SERPINE1 554 1.6727143.6487641.6391258.94139736 1.2942226.3671 PTPMT1 114971.94817686 -.5321423.22488.9815246.98996523.4151 RFTN1 2318.96252831 -.3819957.43859.88927916 1.4179474.5328 AXL 558.941354985 -.643497.4288594.86546369 1.23918.5535 ERRFI1 5426 1.62187922.633858.4556523.9714441 1.16141265.6228 COX8A 1351 1.89728221.85928327.2626111 1.35583 1.1472861.639 FGF2 2247.827753134 -.189432.5985238.73612979.93785.713 DUT 1854.988714113 -.11356.2434486.94264539 1.37343.8411 MYLK 4638 1.43757681.42827357.5129596.94392283 1.15415166.996 F3 2152.88345341 -.21276591.6478146.71195879.9177891.1827 CNP 1267.99947665 -.52353.2183194.95761128 1.4317222.153 CDK14 5218.93518815 -.1145834.429461.83584.98286283.16297 YAP1 1413 1.74151146.7153718.345597 1.38216 1.1494337.2713 FSTL1 11167 1.31786658.31291919.4585214.9431597 1.128863.36856 KIAA133 23325.958991192 -.4187339.2376679.91534389 1.471977.53691 LLGL1 3996 1.751845.72491857.2716521 1.1943547 1.13398128.5473 DRAM2 128338.964263149 -.363915.2473698.91862744 1.1216596.63421 PDLIM2 64236.937252649 -.64824.348325.875421 1.347318.79515 KLF6 1316.976919217 -.2335132.3523937.91172287 1.4677769.11534 GLTSCR1 29998.9584414 -.429289.2555494.9112293 1.72973.13131 BICC1 8114 1.12122364.11441773.727945.9735198 1.29135341.239443 FAM45A 44636.9863748 -.14699.298648.946318 1.2744154.24316 CCRN4L 25819 1.964242.925365.3776258 1.18272 1.1864826.273882 CAMK4 814.953738647 -.473656.585836.852828 1.6978221.32353 CYR61 3491 1.44917475.43937911.553632.93757316 1.16455182.348566 PFKFB3 529.965791 -.429391.42334.884859 1.435446.368723 CTGF 149 1.21113128.2893334.583639.91132481 1.14412777.449523 PRKACG 5568 1.38285.3813569.128564.97884252 1.2943659.663378 ATP6V1A 523 1.433343.432467.2194855.9624477 1.484898.76478
Table S4, Related to STAR methods. qpcr primer list Gene Forward Reverse Abhd4 5'-AAGCTAGCTCTTCCCGATGC-3' 5'-TCTCCTACCCATGCCTTGTC-3' Actb 5 -ATCCGCCGCCCGTCCACA-3 5 -ACCATCACGCCCTGGTGCCT-3 ACTB 5 -ATCCGCCGCCCGTCCACA-3 5 -ACCATCACGCCCTGGTGCCT-3 Bax 5'-TGAAGACAGGGGCCTTTTTG-3' 5'-AATTCGCCGGAGACACTCG-3' Cdkn1a 5'-CTAGGGGAATTGGAGTCAGG-3' 5'-AGAGACAACGGCACACTTTG-3' Crip2 5'-GGCCAGGTCTGGGATTTC-3' 5'-TCATGGAGAAATACGTGTCACC-3' Phlda3 5'-GAGCGGTGGAACATGTAAGG-3' 5'-TCGTGCGATGCTACTCTCTC-3' Ptpn14 5 -AGCACTACTCGGAGACCCAT-3 5 -GAGAACGGCAGTACAAGGCT-3 PTPN14 5 -CGACTTCTGGCAGATGGTGT-3 5 -GTGGCTTTTGGTTCGTCCAC-3